The major objective and long-range goal of this research program is investigation of the microstructure of the macular region of the human retina, including changes which may take place as a result of senescence. The macula is significant because (1) it is the site of greatest visual acuity, and (2) it is affected by age-associated macular degeneration (AMD)--a major cause of blindness in our society. By means of light and electron microscopic examination of human retinas from individuals representing all stages of the human life span, the microstructure of the visual cells, retinal pigment epithelium (RPE), and Bruch's membrane will be analyzed throughout the macula, by quantitative means, with particular emphasis on the fovea. The dimensions of individual pigment epithelial cells and the concentration of rods and cones will be assessed in different regions of the macula at different ages. This will make it possible to determine the number of rods and cones associated with each RPE cell, and will reveal whether or not there is an age-associated loss of any of these cells. The interrelationships of RPE residual bodies, basal laminar deposits, drusen and contamination of Bruch's membrane will be studied with the aim of elucidating the etiology of AMD. Animal experiments involving autoradiography will investigate (1) renewal of the RPE cell basal lamina and Bruch's membrane, (2) age changes in the rate of rod outer segment membrane formation, (3) species differences in the ratio of photoreceptors to RPE cells, and (4) the loss of visual cells and RPE cells in old animals.